67 research outputs found
The Dynamics of Ca2+ Ions within the Solvation Shell of Calbindin D9k
The encounter of a Ca2+ ion with a protein and its subsequent
binding to specific binding sites is an intricate process that cannot be fully
elucidated from experimental observations. We have applied Molecular Dynamics to
study this process with atomistic details, using Calbindin D9k (CaB) as a model
protein. The simulations show that in most of the time the Ca2+
ion spends within the Debye radius of CaB, it is being detained at the 1st and
2nd solvation shells. While being detained near the protein, the diffusion
coefficient of the ion is significantly reduced. However, due to the relatively
long period of detainment, the ion can scan an appreciable surface of the
protein. The enhanced propagation of the ion on the surface has a functional
role: significantly increasing the ability of the ion to scan the protein's
surface before being dispersed to the bulk. The contribution of this mechanism
to Ca2+ binding becomes significant at low ion concentrations,
where the intervals between successive encounters with the protein are getting
longer. The efficiency of the surface diffusion is affected by the distribution
of charges on the protein's surface. Comparison of the Ca2+
binding dynamics in CaB and its E60D mutant reveals that in the wild type (WT)
protein the carboxylate of E60 function as a preferred landing-site for the
Ca2+ arriving from the bulk, followed by delivering it to
the final binding site. Replacement of the glutamate by aspartate significantly
reduced the ability to transfer Ca2+ ions from D60 to the final
binding site, explaining the observed decrement in the affinity of the mutated
protein to Ca2+
Immunosenescence and lymphomagenesis
One of the most important determinants of aging-related changes is a complex biological process emerged recently and called \u201cimmunosenescence\u201d. Immunosenescence refers to the inability of an aging immune system to produce an appropriate and effective response to challenge. This immune dysregulation may manifest as increased susceptibility to infection, cancer, autoimmune disease, and vaccine failure. At present, the relationship between immunosenescence and lymphoma in elderly patients is not defined in a satisfactory way. This review presents a brief overview of the interplay between aging, cancer and lymphoma, and the key topic of immunosenescence is addressed in the context of two main lymphoma groups, namely Non Hodgkin Lymphoma (NHL) and Hodgkin Lymphoma (HL). Epstein Barr Virus (EBV) plays a central role in the onset of neoplastic lymphoproliferation associated with immunological changes in aging, although the pathophysiology varies vastly among different disease entities. The interaction between immune dysfunction, immunosenescence and Epstein Barr Virus (EBV) infection appears to differ between NHL and HL, as well as between NHL subtypes
Performance-based vs socially supportive culture:a cross-national study of descriptive norms and entrepreneurship
This paper is a cross-national study testing a framework relating cultural descriptive norms to entrepreneurship in a sample of 40 nations. Based on data from the Global Leadership and Organizational Behavior Effectiveness project, we identify two higher-order dimensions of culture – socially supportive culture (SSC) and performance-based culture (PBC) – and relate them to entrepreneurship rates and associated supply-side and demand-side variables available from the Global Entrepreneurship Monitor. Findings provide strong support for a social capital/SSC and supply-side variable explanation of entrepreneurship rate. PBC predicts demand-side variables, such as opportunity existence and the quality of formal institutions to support entrepreneurship
Pan-cancer analysis of whole genomes
Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe
How to combat cyanobacterial blooms: strategy toward preventive lake restoration and reactive control measures
Demographic and socio-economic differences in financial information literacy among university students
Spatially resolved and orientation dependent Raman mapping of epitaxial lateral overgrowth nonpolar a-plane GaN on r-plane sapphire
Identification of respiratory virus in infants with congenital heart disease by comparison of different methods
Respiratory virus infections are the main cause of infant hospitalization and are potentially severe in children with congenital heart disease (CHD). Rapid and sensitive diagnosis is very important to early introduction of antiviral treatment and implementation of precautions to control transmission, reducing the risk of nosocomial infections. In the present study we compare different techniques in the diagnosis of respiratory viruses in CHD infants. Thirty-nine samples of nasopharyngeal aspirate were obtained from CHD infants with symptoms of respiratory infection. The Multiplex PCR (Seeplex® RV 12 ACE Detection) driven to the detection of 12 respiratory viruses was compared with the direct immunofluorescence assay (DFA) and PCR, both targeting seven respiratory viruses. The positivity found by DFA, Multiplex and PCR was 33.3%, 51.3% and 48.7%, respectively. Kappa index comparing DFA and Multiplex, DFA and PCR and PCR and Multiplex PCR was 0.542, 0.483 and 0.539, respectively. The concordance between techniques was considered moderate. Both Multiplex PCR (p = 0.001) and PCR (p = 0.002) detected significantly more respiratory virus than DFA. As the performance of the tests may vary, the combination of two or more techniques may increase diagnostic sensitivity favoring the diagnosis of co-infections, early introduction of antiviral therapy and implementation of appropriate measures
Controversies in Enucleation Technique and Implant Selection: Whether to Wrap, Attach Muscles, and Peg?
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